Distinct mitotic dynamics and neuronal migration patterns between gyri and sulci in the ferret neocortex during cortical folding

Abstract

Neocortical folding (i.e., gyrification) is a key evolutionary and developmental feature of the brain, facilitating cortical surface expansion and enhanced cognitive function. However, the precise strategies and mechanisms underlying cortical folding remain incompletely understood. In this study, we systematically investigated the dynamic formation of neocortical folding in the ferret. Our findings reveal significant differences in neurogenesis and neuronal migration between the developing lateral gyrus (LG) and adjacent lateral sulcus (LS) of the ferret neocortex. Specifically, progenitors in the LG exhibited higher mitosis activity and a shorter S-phase duration compared to those in the LS. Additionally, immature neurons in the LG followed a fan-like migration pattern, whereas those in the LS exhibited a flower bud-like pattern. Organotypic slice cultures and time-lapse imaging further demonstrated that the migration trajectory of immature neurons to the neocortex is more straightforward in the LG than in the LS. Together, these results highlight distinct cellular behaviors between the developing gyrus and sulcus, providing novel insights into cellular mechanisms underlying cortex folding.